Fully automated diagnostic analyzers are commercially available to perform chemical assays and immunoassays of biological fluids such as urine, blood serum, plasma, cerebrospinal liquids and the like. Generally, reactions between an analyte in a patient sample and reagents used during the assay result in generating some sort of signal that can be measured by the analyzer. From this signal the concentration of analyte in the patient sample may be calculated. Such automated analyzers generally use an aspirating means such as a sampling tip, or probe or needle, to transfer desired volumes of liquid samples or liquid reagents between receptacles, such as between sample containers, reagent containers and reaction cuvettes disposed on the analyzer. Hereinafter, variations of the term aspirate refer to all of such processes for extracting liquid from one container and depositing at least some of the liquid into the same or another container and further includes the supporting devices required to complete the liquid handling operations.
Aspirators typically comprise an elongated, needle-like probe or pipette having a hollow passage whereby liquid may be aspirated into and/or dispensed from the probe using appropriate pumping resources. The pipette may be carried by a transport mechanism adapted to provide horizontal and vertical movement so as to enable the pipette tip to be lowered into a liquid in a reservoir for aspiration of the liquid, and for transporting the liquid to a another location whereat the pipette is lowered to an optimal position for dispensing the liquid. Some type of device, such as a piston assembly, which may be incorporated into the pipette, is operated electronically to aspirate liquid into the pipette and to dispense liquid from the pipette using vacuum pressures.
It is desirable, when aspirating a liquid, to accurately determine if any abnormalities or non-uniformities within the liquid have adversely affected the overall quality of the aspiration process. Non-uniformities such as clots, bubbles, foam, insufficient volume, etc, may exist in liquids, particularly when the liquid is one of several body fluids being analyzed as these frequently are of a non-uniform composition. Various methods have been developed to detect the effect of such non-uniformities on the aspiration process.
U.S. Pat. No. 6,370,942 discloses an method for evaluating the quality of a liquid aspiration for undesirable events such as partial or complete clogs, or aspiration of air by employing three separate aspiration tests including a pressure difference test to verify liquid was aspirated, a pressure recovery test to check for clogs and aspiration of unwanted cells, and a pressure shape test to check for abnormalities during aspiration, such as clogs, air aspiration, density changes (due to aspiration of blood cells), etc. Three algorithms are employed, and each must produce a positive result for the sample to be released for transfer elsewhere.
U.S. Pat. No. 6,022,747 discloses a blood clot detector having a pressure transducer on an aspiration line to provide output voltage data to a microprocessor corresponding to the vacuum level during aspiration. The microprocessor integrates the vacuum readings over time during the aspiration cycle to provide a pressure integral for each test sample aspiration. A pressure integral is determined for an unclotted aspiration and is used as a reference for comparison with the pressure integrals of each test sample aspiration to determine whether a blood clot has interfered with the test sample aspiration. Acceptability of the test sample for analysis is based upon a predetermined difference between the reference pressure integral and each test sample pressure integral.
U.S. Pat. Nos. 5,814,275, 5,622,869 and 5,451,373 relate to an apparatus for detecting obstructions of a flow line. A pressure detector detects changes in pressure within a flow cavity, indicating the presence of an obstruction. A barrier is disposed near the pressure detector so that when said flow line and pressure detector expand, the rigid barrier does not expand and the pressure detector is compressed.
U.S. Pat. No. 5,540,081 relates to a pipetting apparatus provided with clot detection comprising a nozzle for aspirating a sample. A pressure sensor and a plurality of pressure difference calculating circuits obtain a pressure difference at a different pressure calculation period. A plurality of discriminating circuits each having a different discrimination threshold value determined according to each of the pressure calculation. An alarm circuit is included for outputting a clot detection alarm signal when at least one of said discriminating circuits discriminates that the obtained pressure difference exceeds the discrimination threshold value.
U.S. Pat. No. 5,503,036 relates to an obstruction detection circuit for detecting an obstruction of a sample probe of an automated fluid sample aspiration/dispensation device and a method for detecting such an obstruction. In one embodiment, the obstruction detection circuit includes a pressure sensor measuring the pressure in a fluid conduit connecting a pump and to a sample probe orifice. The pressure within the connecting fluid conduit is measured shortly after the start of the aspiration or dispensation of a sample volume by the automated fluid sample aspiration-dispensation device. The pressure within the connecting fluid conduit is again measured after the completion of the aspiration or the dispensation by the pump, and if the pressure has not returned to a predetermined range within a predetermined amount of time, an error condition is reported.
U.S. Pat. No. 5,463,895 discloses provides an apparatus and method of detecting non-homogeneity in a fluid sample, such as the presence of foam or bubbles on the surface of the sample, and/or the presence of clots on the surface or in the bulk of the sample. This method involves determining the ambient air pressure within a pipettor, aspirating air into the pipettor as the pipettor moves towards a sample in container and monitoring for a pressure change in the pipettor to indicate the surface level of the fluid in said container. The pipettor is immersed in the fluid and a volume of fluid is withdrawn from the container; pressure changes are monitored after aspiration and compared to predetermined normal aspiration pressure windows.
Liquid aspiration quality determining processes like described are not satisfactory in all instances. For example, many systems for determining the quality or integrity of an aspiration process depend on measuring differences in vacuum pressure at different pre-determined intervals during the aspiration process and comparing a vacuum pressure values to a range of predetermined satisfactory values. Other systems compare derivatives of a vacuum pressure profile to a range of predetermined satisfactory values. As the state of the art advances, aspirated sample volumes become smaller and smaller, causing pressure differential values for liquids with different viscosities become more erratic or “noisy”. In addition, pressure profiles of certain higher viscosity liquids do not reach stable end-point values. Hence, there is a need for an improved method for determining the quality of a liquid aspiration process that is effective for small aspiration volumes that may contain an unwanted clot or be insufficient, in the instance of a “short sample”.